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Inquiry Question: How extensive is the impact of Dengue Fever (first infection) on Thalassemia Major sufferers?
Abstract:
The purpose of this report is to determine the potential impact of Dengue Fever symptoms (first infection) when presented Thalassemia Major. To determine this potential impact, a thorough research analysis was conducted into Dengue Fever (effect on body, immune response, prevention and treatment) and of Thalassemia Major (cause, prevention and current medical management). By establishing similarities and conditions induced by each disease, as well as using case studies, it was hypothesised that Thalassemia could worsen the conditions of Dengue Fever.
How does Dengue Fever affect the body?
Cause and Transmission
Dengue Fever is a non-contagious, arbovirus infectious disease caused by one of four dengue serotypes (DENV-1 to DENV-4); the path of transmission through infected Aedes aegypti, Aedes albopictus females, thus not being contagious (i.e. vector-borne). Dengue Fever impairs the haemostasis and coagulation function platelets, which leads to complications such as thrombocytopenia, uncontrolled bleeding and low blood pressure (Symptoms-Figure 1).
Human Immune Response
During extrapolation of human blood, infected mosquitoes transmit the virus past the first line of defence, immediately causing cell damage. Damaged cells subsequently release chemokines and histamines, initiating the vasodilation of blood vessels and subsequent diapedesis of responding non-specific leukocytes toward the site of infection as well as inducing fever (inflammation). In extreme cases Dengues infection of Langerhans Cells can exacerbate the infection, which allows virus to spread through the lymphatic system, potentially resulting in viremia. Macrophages that partially ingest virus will with MHC II [1] present the protein fragment on plasma membrane, then initiates B and T lymphocyte production.
Successfully binding immunoglobulin simultaneously hinder viral activity whilst opsonising viral material for phagocytosis, which with the MHC II complex attracts and activates antigen specific CD4+ T cells. Activated CD4+ cells subsequently undergo mitosis to produce memory and effector cells; effector cells are plasma cells that mass produce free antibodies which are able to uniquely bind externally onto the E glycoprotein. MHC I [2] complex within infected cells bind on to antigen material within the cell, present them to the surface and attract the antigen specific CD8+ T cell, thus initiating the mitosis into effector and memory cells. Cytotoxic T cells then engage in an immuno-synapse, subsequently releasing chemicals inducing death of infected cell.
Current Prevention and Medical Treatment
Currently, there is no direct cure for Dengue Virus. The best preventative measure is to reduce the human exposure to mosquitoes and reducing mosquito density. Reducing mosquito density involves measures that reduce breeding grounds within residential areas, such as concrete depressions and vases. Suggestions include wearing protective garments, well-screening homes and using insect repellent. (Figure 3). In managing Dengue once infected, fluid monitoring and balance is advised (hospitalisation). Hemoconcentration could be used as guideline for fluid replacement therapy.
Thalassemia
How does Thalassemia Major affect the human body?
Haemoglobin (Figure 4) within a healthy person is a spherical unit composed of four (4) polypeptide chains held together by noncovalent interactions. Within each of the four folded polypeptide chains hold complex porphyrin units (haems); haems four nitrogens bind to a charged iron molecule in the centre of the porphyrin ring, which binds to oxygen (Figure 5).
Thalassemia is an inherited autosomal recessive disorder (Figure 6) caused single gene affecting proteins making up haemoglobin within the erythrocytes. The causation of Thalassemia is dependent of both parents genetics. Thalassemia could also refer to the underproduction of globin protein, deformity and subsequent destruction of erythrocyte by the spleen, causing anaemia. As protein chains are coded by DNA, missing aspects of that code specifically for each of the four chains making up haemoglobin would result in a missing chain, and the attached haem, thus reducing the amount of oxygen carried. Alpha Thalassemia is the condition where alpha chains within haemoglobin are missing. Similarly, Beta Thalassemia is the condition where beta chains within haemoglobin are missing.
Current Prevention
As this disease is an inherited genetic disorder, counselling could be an alternative to prevent some cases of developing Thalassemia Major. Two available prenatal tests are Chorionic Villus Sampling [3] and Amniocentesis [4].
Current Treatment
In addition to the importance of healthy diet, avoiding infections and intake of excess iron, Thalassemia Major sufferers require frequent blood transfusion and iron management (supplements). An extreme measure to reducing frequent blood transfusion would be splenectomy, reducing anaemia level removal of erythrocyte. Alternatively, children with severe Thalassemia can also undergo bone marrow transplant that can potentially eliminate lifelong blood transfusion and iron management.
Links and Interaction
Both Thalassemia Major and Dengue Fever affect the same aspect of human body (although Thalassemia affects erythrocyte whilst Dengue Fever affects platelets and damages blood vessels), that being the circulation system. One condition of Thalassemia Major is the prevalence of anaemia complications (impaired erythrocytes such as iron deficiency) and subsequent reduction of erythrocytes, requiring blood transfusion. By adding Dengues modulation impairing platelets coagulation, the chance of someone who suffers both Dengue and Thalassemia Major simultaneously whilst left untreated could impede their chance of survival from added complications, such as iron overload and liver impairment [5]. Complications noted This is despite comparative observations [6] made that Thalassemia had no impact in the immune response to Dengue Fever.
Two studies from Thailand explicitly studied the links and interaction of Dengue and Thalassemia, where they compared clinical manifestations of non-Thalassemia sufferers with Thalassemia sufferers when clinically presented. Both studies observed unusual clinical manifestation that Thalassemia sufferers had, where close to none had hemoconcentration, but rather anaemia with low haematocrit level [7]. Hemoconcentration is the phenomenon of plasma diapedesis and blood vessel permeability due to interstitial fluid loss. Misdiagnosis of Dengue cases involving Thalassemic patients could be overlooked, due to the presence of hemoconcentration in dengue fever. Furthermore, the lack of hemoconcentration would hamper the fluid replacement therapy.
From the study results, it is imperative for Thalassemia Major sufferers to receive special treatment when managing Dengue Fever, given the likeness and seriousness of complications related to Thalassemia-induced deficiencies.
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